Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury

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dc.contributor.authorLamas Paz, Arantza
dc.contributor.authorMorán, Laura
dc.contributor.authorSalinas Rodríguez, Beatriz
dc.contributor.authorLópez Alcántara, Nuria
dc.contributor.authorAsensio, Iris
dc.contributor.authorFengjie, Hao
dc.contributor.authorKang, Zheng
dc.contributor.authorMartín Adrados, Beatriz
dc.contributor.authorMoreno Gutiérrez, Laura
dc.contributor.authorCogolludo Torralba, Ángel Luis
dc.contributor.authorGómez Del Moral Martín-Consuegra, Manuel María
dc.contributor.authorMartínez Naves, Eduardo
dc.contributor.authorVaquero Martín, Francisco Javier
dc.contributor.authorBañares Cañizares, Rafael
dc.contributor.authorNevzorova, Yulia
dc.contributor.authorCubero Palero, Francisco Javier
dc.date.accessioned2024-01-11T07:59:36Z
dc.date.available2024-01-11T07:59:36Z
dc.date.issued2020-12-21
dc.description.abstractBinge drinking, i.e., heavy episodic drinking in a short time, has recently become an alarming societal problem with negative health impact. However, the harmful effects of acute alcohol injury in the gut-liver axis remain elusive. Hence, we focused on the physiological and pathological changes and the underlying mechanisms of experimental binge drinking in the context of the gut-liver axis. Eight-week-old mice with a C57BL/6 background received a single dose (p.o.) of ethanol (EtOH) [6 g/kg b.w.] as a preclinical model of acute alcohol injury. Controls received a single dose of PBS. Mice were sacrificed 8 h later. In parallel, HepaRGs and Caco-2 cells, human cell lines of differentiated hepatocytes and intestinal epithelial cells intestinal epithelial cells (IECs), respectively, were challenged in the presence or absence of EtOH [0-100 mM]. Extracellular vesicles (EVs) isolated by ultracentrifugation from culture media of IECs were added to hepatocyte cell cultures. Increased intestinal permeability, loss of zonula occludens-1 (ZO-1) and MUCIN-2 expression, and alterations in microbiota-increased Lactobacillus and decreased Lachnospiraceae species-were found in the large intestine of mice exposed to EtOH. Increased TUNEL-positive cells, infiltration of CD11b-positive immune cells, pro-inflammatory cytokines (e.g., tlr4, tnf, il1β), and markers of lipid accumulation (Oil Red O, srbep1) were evident in livers of mice exposed to EtOH, particularly in females. In vitro experiments indicated that EVs released by IECs in response to ethanol exerted a deleterious effect on hepatocyte viability and lipid accumulation. Overall, our data identified a novel mechanism responsible for driving hepatic injury in the gut-liver axis, opening novel avenues for therapy
dc.description.departmentDepto. de Medicina
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía, Comercio y Empresa
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipGerman Research Foundation
dc.description.statuspub
dc.identifier.citationLamas-Paz A, Morán L, Peng J, Salinas B, López-Alcántara N, Sydor S, Vilchez-Vargas R, Asensio I, Hao F, Zheng K, Martín-Adrados B, Moreno L, Cogolludo A, Gómez Del Moral M, Bechmann L, Martínez-Naves E, Vaquero J, Bañares R, Nevzorova YA, Cubero FJ. Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury. Front Pharmacol. 2020 Dec 21;11:603771. doi: 10.3389/fphar.2020.603771
dc.identifier.doi10.3389/fphar.2020.603771
dc.identifier.issn1663-9812
dc.identifier.officialurlhttps://www.frontiersin.org/articles/10.3389/fphar.2020.603771/full
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/33408632/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/92415
dc.issue.numberDiciembre 2020
dc.journal.titleFrontiers in Pharmacology
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.projectIDSAF2016-78711
dc.relation.projectIDSAF2017-87919-R
dc.relation.projectIDEXOHEP-CM S2017/BMD-3727
dc.relation.projectIDNanoLiver-CM Y2018/NMT-494
dc.relation.projectIDERAB Ref. EA 18/14,AMMF 2018/117
dc.relation.projectIDUCM-25-201
dc.relation.projectIDCOST ActionCA17112
dc.relation.projectIDFB/TRR57/P04
dc.relation.projectIDSFB 1382-403224013/A02
dc.relation.projectIDDFG NE 2128/2-1
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu611.081.1
dc.subject.keywordAlcohol (EtOH)
dc.subject.keywordExtracellular vesicles
dc.subject.keywordGut-liver axis
dc.subject.keywordHepatocytes
dc.subject.keywordIntestinal epithelial cells
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco2407 Biología Celular
dc.titleIntestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number11
dspace.entity.typePublication
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